14-91126957-A-T

Variant names:

• chr14-91126957-A-T
• rs7146008
• NM_001102368.3:c.-82+12674A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001102368.3(DGLUCY):​c.-82+12674A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 151,426 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00026 (1 hom., cov: 29)
• Consequence: DGLUCY NM_001102368.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850
• Publications: 12 publications found

Genes affected

DGLUCY (HGNC:20498): (D-glutamate cyclase) Predicted to enable D-glutamate cyclase activity. Predicted to be involved in glutamate metabolic process. Predicted to be located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102368.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGLUCY	NM_001102368.3	MANE Select	c.-82+12674A>T		intron	N/A	NP_001095838.1	Q7Z3D6-2
	DGLUCY	NM_001286470.2		c.-532+12429A>T		intron	N/A	NP_001273399.1	Q7Z3D6-2
	DGLUCY	NM_001358310.2		c.-81-30682A>T		intron	N/A	NP_001345239.1	Q7Z3D6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGLUCY	ENST00000256324.15	TSL:1 MANE Select	c.-82+12674A>T		intron	N/A	ENSP00000256324.9	Q7Z3D6-2
	DGLUCY	ENST00000522322.5	TSL:1	c.-175+11963A>T		intron	N/A	ENSP00000427953.1	Q7Z3D6-1
	DGLUCY	ENST00000523771.5	TSL:1	c.-82+11736A>T		intron	N/A	ENSP00000429655.1	Q7Z3D6-1

Frequencies

GnomAD3 genomes AF: 0.000264 AC: 40 AN: 151426 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000264 AC: 40 AN: 151426 Hom.: 1 Cov.: 29 AF XY: 0.000271 AC XY: 20 AN XY: 73842

African (AFR) AF: 0.00 AC: 0 AN: 41162

American (AMR) AF: 0.00 AC: 0 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 136380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.11
DANN	Benign	0.62
PhyloP100		-0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7146008; hg19: chr14-91593301;